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However, the evidence has not been appraised critically. We carried out a systematic review and meta-analysis of studies of cellular calcium indices in bipolar disorder. 2281 records were identified and 117 screened, of which 32 were eligible and 21 were suitable for meta-analyses. The latter each involved up to 642 patients and 404 control subjects. We found that basal free intracellular [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] is increased in bipolar disorder, both in platelets and in lymphocytes. The effect size is 0.55, with an estimated elevation of 29%. It is observed in medication-free patients. It is present in mania and bipolar depression, but data are equivocal for euthymia. Cells from bipolar disorder individuals also show an enhanced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] response to stimulation with 5-HT or thrombin, by an estimated 25%, with an effect size of 0.63. In studies which included other diagnoses, intracellular basal [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] was higher in bipolar disorder than in unipolar depression, but not significantly different from schizophrenia. Functional parameters of cellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    (e.g. calcium transients), and neuronal [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ], have been much less investigated, and no firm conclusions can be drawn. In summary, there is a robust, medium effect size elevation of basal and stimulated free intracellular [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] in bipolar disorder. The results suggest altered calcium functioning in the disorder, and encourage further investigations into the underlying mechanisms, and the implications for pathophysiology and therapeutics.\n                  <\/jats:p>","DOI":"10.1038\/s41380-019-0622-y","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T15:03:56Z","timestamp":1575471836000},"page":"4106-4116","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Cellular calcium in bipolar disorder: systematic review and meta-analysis"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-1126","authenticated-orcid":false,"given":"Paul J.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3393-3494","authenticated-orcid":false,"given":"Nicola","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Mould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura","family":"Al-Juffali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Tunbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"622_CR1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/archneurpsyc.1922.02190140070006","volume":"8","author":"PG Weston","year":"1922","unstructured":"Weston PG, Howard MQ. 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